We propose to use a combined neurochemical and anatomical approach (autoradiography) to determine the types, loctions and prevalence of some of the receptors which control pressure, flow and permeability in cerebral vessels, especially in man. We expect to confirm and extend current theories that receptors involved in the control of pressure notably alpha 1, 5-HT and muscarine receptors) are located primarily in meningial vessels, while other receptors involved with the control of flow (alpha 2, beta etc.) are present primarily in smaller intraparenchymal vessels. Our intent to provide further information about normal receptors and to lay the groundwork for investigations of changes in receptor mechanisms wish ischemia, reperfusion, hemorrhage, aging, migraine,the long-term administration of drugs, etc. Methods will be developed utilizing rats, and then applied to human tissue. Primary emphasis is given to new in vitro labelling techniques for autoradiography since this is the only practicable approach for human vessels. Most studies will be by light microscopy since few receptor ligands withstand embedding procedures for electron microscopy. Specific aims are as follows. 1. Frozen sections of large and pial vessels and of isolated microvessels from the rat and man will be exposed in vitro to radioligands for receptors which react with vasoactive amines (norepinephrine, acetylcholine, 5-0hydroxytryptamine, histamine, epinephrine, adenosine). Established autoradiographic techniques will then be used to examine the location and prevalence of the bound ligands alond vessels in rllation to their diameters. In the rat, studies will be repeated after unilateral degeneration of nerves from a superior cervical ganglion, locus ceruleus and/or brainstem raphe nuclei. 2. We will develop a technique for autoradiography of microvessels on filters so as to better relate precise binding data obtained in vitro, with autoradiographic data. 3. Attempts will be made to label nerves in freshly isolated microvessels with radioactive amines before autoradiography, to better characterize the innervation of small vessels in man. 4. Muscarine receptors will be localized within vessel walls with a covalently-bound ligand, by electron microscopic autoradiography.